For three decades research and development work in the laboratories of Worley and co-workers has proceeded with the goal of producing novel antimicrobial compounds (for example, see review articles Worley, S. D., Williams, D. E., “Halamine Water Disinfectants”, CRC Crit. Rev. Environm. Cntrl. 1988, 18, 133; Worley, S. D., Sun, G., “Biocidal Polymers”, Trends Polym. Sci. 1996, 4, 364; Kenawy, E., Worley, S. D., Broughton, R. M., “The Chemistry and Applications of Antimicrobial Polymers, A State of the Art Review”, Biomacromolecules 2007, 8, 1359, and the references incorporated therein). All of the work has focused upon a class of compounds known as organic N-halamines which are generally heterocyclic monomers or polymers containing nitrogen-halogen bonds. The most stable of these compounds with regard to the release of bleaching free halogen in aqueous solution are those containing N—Cl covalent bonds stabilized by electron-donating substituents, e.g. alkyl groups such as methyl groups, attached to the carbon atoms in the cyclic structures directly linked to the nitrogen atom containing the chlorine atom. The mechanism by which these N-halamine compounds inactivate pathogenic microorganisms is through a direct contact in which the N-halamine donates its halogen atom to the biological cell, wherein the cell is inactivated through an oxidation process. If the N—Cl bond on the N-chloramine is sufficiently strong, the disinfection process will be slower than for “free chlorine”, the antibacterial agent which is present in household bleach. However, if free chlorine is not appreciably released from an N-chloramine into aqueous media, then undesirable chemical processes such as corrosion and bleaching will be minimized.
There is a need for soaking formulations which can be used to maintain disinfection of contact lenses so as to prevent eye infections in the wearer. Any cyclic N-chloramine will be useful in this regard, particularly if it is supplemented by an oxidant such as sodium chlorite so as to accentuate the inactivation process kinetics. For example, the N-halamine, 1-chloro-2,2,6,6-tetramethyl-4-piperidinol, has been demonstrated to inactivate pathogens which are important in ophthalmic uses (see Carey, et al., US 2010/0303930 A1 and Worley, et al., Provisional application Nos. 61/065,320 filed on Feb. 11, 2008, 61/153,665, filed on Feb. 19, 2009, and 61/305,747 filed on Feb. 18, 2010). However, this compound at concentrations necessary for adequate disinfection releases sufficient free chlorine into contact lens soaking formulations to bleach out the dyes incorporated into the contact lenses which are necessary for tinting and ultraviolet protection, rendering the compound of little use for contact lens applications.